Dr. Joachim Baehring, Treating and Living with a
Brain Tumor January 3, 2010

Welcome to Yale Cancer Center Answers with Drs. Ed Chu and
Francine Foss, I am Bruce Barber. Dr. Chu is Deputy Director
and Chief of Medical Oncology at Yale Cancer Center and Dr. Foss is
a Professor of Medical Oncology and Dermatology specializing in the
treatment of lymphomas. If you would like to join the
conversation, you can contact the doctors directly. The
address is canceranswers@yale.edu and
the phone number is 1888-234-4YCC. This evening, Ed welcomes
Dr. Joachim Baehring. Dr Baehring is Director of the Yale
Cancer Center Brain Tumor Program and he is an Associate Professor
of Neuro-oncology. Here is Ed Chu.

Chu
Why don't we start off by defining what brain cancer is?

Baehring
Essentially there are 2 types of brain cancer. Primary brain
cancers are cancers that arise directly in the brain, and then
there are metastatic brain cancers, which means cancer lesions have
arisen in the brain as metastasis from a systemic tumor elsewhere
in the body.

Chu
For today's discussion we are going to be focusing on that first
type of brain cancer called primary brain cancer. But let's follow
up with, what are the types of other cancers that commonly spread
to the brain?

Baehring
You mean systemic cancers?

Chu
Yeah, the metastatic cancer type.

Baehring
The most common cancers that spread to the brain are breast cancer
and lung cancer, and at the same time those are the most common
cancers in general. Other cancer that is overall less common,
but may have a high risk of seeding to the brain, for example, is
malignant melanoma.

Chu
So getting back to primary brain cancer, how common is it? About
how many patients each year are given this diagnosis of primary
brain cancer? Then I guess within primary brain cancer, there are a
number of different types of subcategories.

Baehring
Right, there are a large number of subcategories. Overall,
there are about 45,000 cases of primary brain tumors in the United
States; that does not equal brain cancer. That includes
benign tumors, cancerous tumors, and malignant tumors, if you
will. The most common primary brain cancer is called
glioblastoma multiforme, and there are about 8,000 to 10,000 cases
in the US per year, and that compares to over 100,000 cases of
colon cancer, and over 200,000 cases of breast cancer and prostate
cancer, so you can tell brain cancer is rare, fortunately.
There are numerous subtypes, I mentioned glioblastoma which is the
most common one. Another very common brain tumor, which is
benign, is called meningioma. That is a tumor that arises from the
covering of the brain and is generally curable by taking it
out.

Baehring
As with other cancers, brain cancer is usually a disease of older
age, so the older we get the higher the risk is of developing brain
cancer, and that applies to the most common primary brain
cancers. There are exceptions, there are cancers that arise
particularly at young age in childhood. There is a tumor of
the balance center of the brain called medulloblastoma which is
much more common in children than it is in adults, but as a general
rule, the older we are the higher the risk is of developing brain
cancer.

Chu
What do we know about the main risk factors for developing brain
cancer?

Baehring
There are very few that actually have been proven to lead
ultimately to brain cancer, one known risk factor is exposure to
radiation, therapeutic doses of radiation. For example, if someone
suffered from childhood leukemia and underwent radiation treatment
to the whole brain, either for treating leukemia in the brain or
preventing leukemia from seeding to the brain, those patients are
at higher risk later in life to develop a number of brain tumors
including malignant brain cancer. That is really the most solid
risk factor that we know of. There are some other
environmental risk factors that are discussed and have been
investigated numerous times, but the one of most concern is
exposure to cell phones. I think we still do not have very
solid data as to whether the risk for brain cancer has increased in
cell phone users, and I do not think we have a good sense as to how
much cell phone use would be unhealthy. I think as a general
rule it is reasonable to limit the exposure to cell phone or other
phones of electromagnetic waves to a minimum, and use devices that
limit the exposure, but again the link really has not been
established yet.

Chu
It is interesting because I guess there have been earlier studies
to show that in fact, there was an increased risk, but I guess that
was using the old analog cell phones, and it was unclear that the
people were using cell phones quite as frequently as they are now.
It is really pretty amazing at how young in age people are starting
to use cell phones, and they seem to be on it for a long period of
time.

Baehring
That's true, yeah, some people use cell phones as a main device to
make phone calls rather than to just make a quick emergency phone
call on the road, but again, there is no study that would tell us
how much cell phone use is too much, and whether there is an
increased risk to begin with.

Chu
And what about dental x-rays, because I know people have asked me
if they have too many dental x-rays could that put them at
increased risk, is there are any truth to that at all?

Baehring
There is no data that would link plain x-rays for dental procedures
to brain cancer. I think as with everything, we should limit
medical procedures including these x-rays to the absolute
minimum. I

Chu
Is there any genetic component, any genetic basis for brain
cancers, so if someone in the family has had brain cancer, does
that increase the likelihood that a sibling or a child could
develop brain cancer?

Baehring
There are certainly genetic risk factors; however, they are
rare. There are a couple of conditions. The most common
one is called neurofibromatosis, and those patients have a certain
gene defect that renders them susceptible to developing all kinds
of tumors affecting both the peripheral and central nervous
system. In the overall scheme though, the number of patients
who develop brain tumors based on one of those predisposition
syndromes is probably less than 3%. And then again, cancer is
common, so if a patient who has brain cancer has several family
members with a cancer history, that may not be alarming to begin
with. If patients have the same kind of tumor within one
family, only certain types of tumors, and they develop these tumors
at an unusually young age, then one should pursue investigation of
whether predisposition exists within that family.

Chu
In terms of symptoms that an individual might experience, what
should one look out for?

Baehring
Brain tumor symptoms are rather nonspecific. A lot of disease
processes affecting the brain can present with symptoms very
similar to how a brain tumor would present. The two most
common initial presentations are headaches and seizures, so
especially somebody who develops seizures late in life, in the
range of about 40 years of age, lets say, that is somewhat
concerning and generally it suggests that there is a structural
problem within the brain and many a times that is a tumor.
Headaches are obviously amongst the most common symptoms that we go
seek medical advice for and the vast majority of headache causes
are benign ones. In terms of headaches, if a patient wakes up
in the morning with a headache and feels nausea, and then as the
day goes on the headache improves, but then over time
week-after-week, month-after-month, those headaches get worse, that
is the type of headache that is more concerning as opposed to the
tension type headache that we all get, that gets worse at the end
of the day and then the next morning after a good night sleep or
massage it has gone. That really does not raise any
concerns.

Chu
What period of time would you say should one get concerned; if the
headache persists for more than a week or two and does not seem to
get better?

Baehring
Yeah, it also depends a little bit on the intensity, if it is a
mild, dull pain, and the patient had a work out or did some
strenuous work, some heavy lifting, then that kind of activity can
set off a tension type headache, and that can linger on for longer,
but especially if there is progression, no clear

explanation for the headache, after a period of maybe a week or
two, one should at least ask the family doctor for a checkup.

Chu
So the next person that should be seen is the general internist or
the family physician?

Baehring
I think that would be the first doctor to see, and the family
doctor can first of all take a good history and do a thorough
examination and if there are certain concerning features then maybe
that doctor would order the first imaging study, or then refer the
patient for neurologic evaluation, or if there is particular
concern about a tumor then to a neuro-oncologist.

Chu
So, you would recommend from the family physician then seeking
attention directly to a neuro-oncologist specialist like yourself
as opposed to say a more general neurologist?

Baehring
It depends a little bit on the symptoms. Frequently it works
that way. If the patient has a headache that gets worse and
worse and the family doctor already orders an imaging study and
that shows a mass lesion, then patients are referred directly to
us. If the symptoms are a little less clear, let's say the
patient develops some strange sensory loss on one side of the body
or something like that, then frequently the family physician refers
those patients to a general neurologist to rule out neurologic
conditions that are much more common than brain tumors.

Chu
What would be the usual imaging studies, x-ray studies, that would
be done to try to make a diagnosis of brain cancer?

Baehring
The most sensitive and specific test for diagnosing a brain tumor
would be an MRI (magnetic resonance imaging). A CAT scan
serves the purpose of ruling out an acute event that would
constitute an emergency such as stroke or a bleed within the brain,
and sometimes it's used as a screening test to make sure that there
is no major tumor within the brain. But if there is really any
concern then an MRI should be obtained, and those scans are done
with contrast dye, and brain cancer does light up on these studies
and it is fairly easy to diagnose.

Chu
So then say once something suspicious is seen on the MRI or CAT
scan, what would be the next step?

Baehring
If there is concern for a brain tumor then a definitive diagnosis
requires that a piece of tissue is obtained from that lesion and
that requires a neurosurgical consultation. If the tumor can
be removed in its entirety, and it seems to be a tumor that would
best be treated that way, then patients undergo full surgery and
the tumor is removed to the largest possible extent without causing
any injury. If the tumor is of a kind that responds favorably
to chemotherapy, or if the tumor is located in the critical area of
the brain where surgery would lead to a disability, then the
surgical procedure

may be limited to a small biopsy, and in that case, only a small
burr-hole is drilled into the patient's head, and then a small
sample is retrieved with essentially a needle.

Chu
Can you tell us a little bit about how you evaluate patients?

Baehring
Most patients come to me referred by another physician so they do
come with imaging studies, and sometimes I am the one who does the
initial workup, but the evaluation consists of a thorough history
and physical examination and review of the imaging studies.
If a surgical procedure has already been performed, we review the
report first and then refer the entire case essentially to what we
call of a tumor board, which is a multidisciplinary conference that
takes place once a week during which we then review the actual
pathology slides, those sections that are performed after the tumor
tissue has been removed, and then these sections are looked at
under the microscope to determine what type of brain tumor it
is. The treatment plan is then generated by our
multidisciplinary team, the neurosurgeons on that team, the medical
oncologist, the neurologist, the radiation oncologist,
pathologists, doctors specialized on the analysis
of the tumor tissue, and radiologist specialists to interpret
imaging studies.

Chu
Great, and maybe on the other side of the break we can talk a
little bit more about this multidisciplinary approach to treating
patients with brain cancer. We are going to take a short
break for medical minute. Please stay tuned to learn more
information about the evaluation and treatment of brain tumors with
our guest expert Dr. Joachim Baehring from Yale Cancer Center.

Chu
Before the break we were talking about the multidisciplinary
approach to treat patients with brain cancer, and you were telling
us about how your multidisciplinary clinic and tumor board
functions. For those who may have missed the first part of this
interview, can you review all of the different oncology disciplines
that are involved in this clinic and the tumor board
conference?

Baehring
We have two platforms to provide multidisciplinary care. On
one side, we have the multidisciplinary clinic where doctors of
various subspecialties evaluate patients at the same time and at
the same place, and then we have the tumor board, which is a
multidisciplinary conference. In our multidisciplinary
clinic, we have neurosurgeons, we have a medical oncologist, a
neurologist, and a radiation oncologist, and new patients
especially are evaluated at the same time. So, if we get a
referral either for management or as a second opinion, we see these
patients as a team. The tumor board then is a platform where
we can discuss patients in more detail, where we can review the
imaging study with one of our neuroradiologists who is a specialist
on brain tumor imaging, with our neuropathologist, who is the
doctor who analyses the tumor tissue, and then as a group we can
come up with the treatment plan, and that may be a standard
treatment plan with an established treatment regimen, or it may be
a clinical trial.

Chu
And again, maybe you can very briefly review the different types of
treatments that can be offered to patients.

Baehring
Most patients with brain cancer require this multidisciplinary
approach. The first step is usually surgery, which may be
simply to retrieve a small piece of tissue to make the diagnosis,
or remove the entire tumor as a first step of treatment. Then
the second step of treatment depends on the type of tumor that we
encounter, for many tumors combined radiation and chemotherapy is
required. For example, the most common tumor that we talked
about in the first part of the interview, glioblastoma multiforme,
requires both radiation and chemotherapy. The chemotherapy
for that tumor comes in pill form and then treatment is
administered over a six-week block followed by additional
chemotherapy down the line. There are other tumors.
There is a tumor called primary CNS, or central nervous system
lymphoma, which is exquisitely sensitive to chemotherapy. So
those patients usually only undergo a biopsy and then go directly
on to chemotherapy, and there are tumors that are surgically
curable such as meningioma. So these patients do not need the
radiation doctor, or me. And then there are tumors that are
very sensitive to radiation. For example, there is a tumor of
the brain that is called germinoma. It is a germ cell tumor
of the brain and that can be cured with radiation. So you can
see there are algorithms in place for different types of brain
tumors and there is a large number, and every single subdivision is
relatively uncommon.

Chu
Joachim, what is gamma knife? We hear that term used a lot.
Is that a surgical procedure, and when would you consider using
gamma knife as a treatment approach?

Baehring
The name almost implies that it is a surgical procedure, but it is
knifeless, although it is called gamma knife. This is a
radio-surgical procedure. Radio-surgery entails the
administration of a very focused beam of radiation to a defined
area of interest within the brain. So, for example, if

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the patient has a tumor that is very deep in the brain that is not
considered a surgically removable tumor, is not responsive to
chemotherapy, or a tumor that is no larger than about 2/3 to 1 inch
in diameter, that would be an ideal target for a gamma knife
radio-surgery. This is a one-day procedure.
Essentially, patients come into our gamma knife centre, a frame is
attached to the patient's head which assures that patients are in a
defined position within the device and then after very complicated
and careful planning, the radiation boost is administered to that
lesion and that really concludes the treatment, but there is no
cutting involved.

Chu
I have also heard the term CyberKnife used. Is that the same
as gamma knife, or is that slightly different?

Baehring
It is similar, but not the same. Gamma knife, as I
mentioned, requires that a firm frame be attached to the patient's
head to make sure that the x-ray beam is truly administered to the
area that is supposed to be radiated. In the other
techniques, like CyberKnife, there are numerous other techniques
that follow the same principle. The targeting of the x-ray beam is
based on plain x-rays. So, x-rays are taken off the
anatomical area of interest from different angles and then through
a computer algorithm that information is used to guide the x-ray
exactly to the target that is supposed to be radiated. You
call that image-guided sterotactic radio-surgery as opposed to the
frame-based radio-surgery which is gamma knife. Technically,
these are different techniques; however, both serve the purpose of
eradicating a very focused problem. One big difference is
that the image-guided radio-surgery can be used anywhere in the
body as opposed to gamma knife which can only be used in the
head.

Chu
By having such a focused delivery of radiation therapy, that can
help to reduce, minimize, the toxicity as well?

Baehring
Absolutely, first of all, one can administer a higher dose to the
cancer, meaning the cell killing will be more efficient. On
the other side, the beam is so focused that the surrounding tissue
is not exposed to this large dose. So, that is a major
advantage of these radio-surgical procedures compared to standard
radiation.

Chu
Joachim, maybe you can just talk a little bit about the role of
biological targeted therapy. We hear that term used a lot for
the treatment of a wide range of other cancers, but as I understand
it now, targeted therapy has also come to the treatment of brain
cancer.

Baehring
Yeah, that is an extremely exciting area of research, and as you
mentioned, many of these treatment concepts have already found
their place in standard treatment protocols, or clinical
trials. "Targeted therapy" means that tumor cells are
attacked through specific growth promoting, or growth inhibiting
mechanisms. The old fashioned chemotherapeutic agents are
un-targeted; they

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have different targets. Maybe some of the newer agents are
specifically targeted to one specific molecule. For example,
in brain cancer, growth of a brain cancer many times is driven by a
receptor molecule on the surface of the cells. It is called
EGFR, or epidermal growth factor receptor. Now, there are
targeted therapies available that specifically render this receptor
dysfunctional, and thus, decrease the flow of signal through this
growth-promoting pathway. Now, that is not unique to brain
cancer. These drugs were developed first for a lung cancer
and other types of systemic cancer, but many of these treatment
concepts do apply to brain cancer as well. There is another
targeted form of treatment that does not attack the tumor itself;
it attacks the tumor's ability to form new blood vessels. You
call those antiangiogenic therapies and there are numerous
mechanisms at various levels that one can use and that is one of
the most exciting new treatment forms for cancer in general, and
for brain cancer specifically.

Chu
In fact Avastin, which is the main antibody that is used to treat
colon cancer, lung cancer, and breast cancer, as I understand was
recently approved to treat glioma.

Baehring
Yeah, bevacizumab, the brand name is Avastin, targets a molecule
called VEGF, vascular endothelial growth factor protein, that is
required to form new blood vessels by the tumor and that was
approved by the FDA in May of this year for relapse glioblastoma,
meaning glioblastoma that has failed the first line of attack which
is radiation and the chemotherapy with a drug called
temozolomide.

Chu
And how is this drug Avastin handled; are there many side effects
associated with this?

Baehring
It is actually tolerated fairly well. Avastin, and other
drugs within that group, can increase the blood pressure and
sometimes patients have to be started on a medication to lower the
blood pressure. It can have an effect on the kidney, limiting
the dose of the Avastin, and it can cause wound healing problems,
but in general, it is fairly well tolerated across all age groups
that we treat.

Chu
Your group at Yale Cancer Center has been very interested in
developing new approaches to treat brain cancer. Maybe you
can tell us a little bit about what is going on in that area?

Baehring
We have a number of investigators at Yale who are interested in
developing new treatment strategies for brain cancer, and there is
one group that is interested in using viruses, genetically-modified
viruses, to specifically attack and kill brain tumor cells. That is
a group led by a Tony van den Pol, from the department of the
neurosurgery. We have a wonderful department led by Mark
Saltzman, by our medical engineering, and his group is trying to
develop particles, they call them nano-particles because they are
micro particles, that can be administered directly into the brain
and then slowly release a therapeutic agent, may that be a
classical chemotherapy agent

Baehring
In all likelihood one could properly generate nano-particles that
can be given through a vein; however, then one would have to worry
about whether these particles can make it to the brain tumor and
the systemic side effects, side effects to the whole body.
One way to administer these drugs would be through direct infusion
into the brain, so at the time the tumor is taken out, the
neurosurgeon would insert micro-catheters into the normal brain
surrounding the tumor and then the drug would be infused through an
infusion pump through these catheters directly into the brain and
into the brain tumor.

Chu
That is pretty fascinating.

Baehring
It is, it is called convection-enhanced delivery, and we were
involved in one of the earliest clinical trials using this
technique first in humans.

Chu
That is interesting because there are these wafers that contain
chemotherapy that are already approved for treating patients with
brain cancer.

Baehring
That is true. That was really the first concept where
chemotherapy was directly administered into the brain, and Dr.
Saltzman was instrumentally involved in the development of these
wafers. These are dime sized discs, essentially, that are
impregnated with the chemotherapy compound that is called
carmustine or BCNU, and it is attached to the wall of the cavity
that the surgeon creates when he takes out the tumor and then over
the course of a few days, that chemotherapy drug diffuses into the
normal brain surrounding the brain tumor and kills any tumor cells
that were not removed at the time of surgery.

Chu
It is fascinating, and it will be very interesting to hear
more. We will have to get you back for a future show.
Are there any clinical trials that you folks are involved with that
you are particularly excited about?

Baehring
We have a number of clinical trials and we have completed a couple
of trials recently. One used a tumor-directed vaccine,
essentially a vaccine that stimulates the immune system to target
the brain tumor. Another clinical trial used one of those
anti-angiogenic compounds that we talked about earlier, so a drug
that interferes with a tumor's ability to form new blood
vessels. Currently, we just launched a new trial in the
setting of one of the national consortia, the Radiation Therapy

Chu
Great. We look forward to having you back on a future show to
hear more about the progress being made in the trial and all the
exciting research that is going on with your group.

Baehring
It would be my pleasure.

Chu
Until next week, this is Ed Chu from Yale Cancer Center wishing you
a safe and healthy week.

If you have any questions or would like to share your comments,
you can go to yalecancercenter.org where you can also subscribe to
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am Bruce Barber and you are listening to the WNPR Health Forum from
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